Rangkuman Citric Acid PDF

1. Citric Acid Cycle (Krebs Cycle): a) Location and Function: - Occurs in the mitochondrial matrix - Central hub for carbohydrate, fat, and protein metabolism - Main purpose: oxidize acetyl groups from acetyl-CoA to CO2, generating reducing equivalents (NADH and FADH2) b) Steps of the cycle:...

1. Citric Acid Cycle (Krebs Cycle): a) Location and Function: - Occurs in the mitochondrial matrix - Central hub for carbohydrate, fat, and protein metabolism - Main purpose: oxidize acetyl groups from acetyl-CoA to CO2, generating reducing equivalents (NADH and FADH2) b) Steps of the cycle: 1. Acetyl-CoA (2C) + Oxaloacetate (4C) → Citrate (6C) 2. Citrate → Isocitrate (both 6C) 3. Isocitrate → α-Ketoglutarate (5C) + CO2 4. α-Ketoglutarate → Succinyl-CoA (4C) + CO2 5. Succinyl-CoA → Succinate (4C) 6. Succinate → Fumarate (4C) 7. Fumarate → Malate (4C) 8. Malate → Oxaloacetate (4C) c) Key enzymes and their cofactors: - Citrate synthase - Aconitase (requires Fe2+) - Isocitrate dehydrogenase (requires NAD+) - α-Ketoglutarate dehydrogenase complex (requires NAD+) - Succinyl-CoA synthetase (produces GTP) - Succinate dehydrogenase (uses FAD) - Fumarase - Malate dehydrogenase (requires NAD+) d) Energy yield: - Per acetyl-CoA: 3 NADH, 1 FADH2, 1 GTP - NADH → 2.5 ATP in respiratory chain - FADH2 → 1.5 ATP in respiratory chain - GTP → 1 ATP - Total: 10 ATP per acetyl-CoA e) Regulation: - Allosteric inhibition by ATP and NADH - Activation by ADP and NAD+ 2. Glycogenesis: a) Definition: The process of glycogen synthesis from glucose b) Location: Primarily in liver and skeletal muscle c) Steps: 1. Glucose → Glucose-6-phosphate (by hexokinase/glucokinase)  2. Glucose-6-phosphate → Glucose-1-phosphate (by phosphoglucomutase) 3. Glucose-1-phosphate + UTP → UDP-glucose (by UDP-glucose pyrophosphorylase) 4. UDP-glucose + glycogen(n) → glycogen(n+1) + UDP (by glycogen synthase) d) Branching: - α-1,6 glycosidic bonds created by branching enzyme - Transfers a segment of 6-7 glucose residues from a chain of at least 11 residues to a nearby chain e) Primer requirement: - Glycogenin protein acts as the initial primer for glycogen synthesis 3. Glycogenolysis: a) Definition: The breakdown of glycogen to glucose-1-phosphate b) Location: Liver (for blood glucose regulation) and muscle (for local energy needs) c) Key enzymes: - Glycogen phosphorylase: Cleaves α-1,4 glycosidic bonds - Debranching enzyme: Handles α-1,6 branch points d) Steps: 1. Glycogen(n) + Pi → Glucose-1-phosphate + Glycogen(n-1) 2. Glucose-1-phosphate → Glucose-6-phosphate (by phosphoglucomutase) 3. In liver: Glucose-6-phosphate → Glucose (by glucose-6-phosphatase) e) Regulation: - Activated by glucagon and epinephrine (via cAMP) - Inhibited by insulin 4. Glycogen Storage Diseases: a) Von Gierke's disease (Type I): - Deficiency in glucose-6-phosphatase - Accumulation of glycogen in liver and kidney b) Pompe's disease (Type II): - Deficiency in lysosomal α-1,4-glucosidase - Glycogen accumulation in lysosomes c) Cori's disease (Type III): - Deficiency in debranching enzyme - Accumulation of limit dextrin d) Andersen's disease (Type IV): - Deficiency in branching enzyme - Accumulation of abnormal glycogen with few branches e) McArdle's syndrome (Type V): - Deficiency in muscle phosphorylase - Reduced exercise tolerance 5. Hexose Monophosphate Shunt (Pentose Phosphate Pathway): a) Function: Generates NADPH and ribose-5-phosphate b) Location: Cytosol of liver, adipose tissue, adrenal cortex, red blood cells c) Key steps: 1. Glucose-6-phosphate → 6-Phosphogluconolactone (generates NADPH) 2. 6-Phosphogluconate → Ribulose-5-phosphate (generates NADPH and CO2) 3. Non-oxidative interconversions of 3, 4, 5, 6, and 7 carbon sugars 6. Gluconeogenesis: a) Definition: Synthesis of glucose from non-carbohydrate precursors b) Location: Liver and kidney c) Key substrates: Lactate, amino acids, glycerol d) Important enzymes: - Pyruvate carboxylase - Phosphoenolpyruvate carboxykinase - Fructose-1,6-bisphosphatase - Glucose-6-phosphatase e) Regulation: - Stimulated by glucagon and cortisol - Inhibited by insulin